An active area of research in population genetics concerns the hypothesis that adaptive evolutionary changes reflect modifications in the level or timing of the expression of structural genes more than changes in the structural genes themselves or their translational products. This hypothesis suggests that variation of genetic elements involved in gene regulation would play a more significant role in evolution and adaptation than structural gene variation. This proposal will initiate a natural population genetics study on gene regulation to evaluate this hypothesis, using as a model the rosy-xanthine dehydrogenase (XDH) system in Drosophila melanogaster. The adaptive potential of XDH activity variation is indicated by the well-documented observations of files that are either deficient or low in XDH activity not surviving under certain environmental conditions. The project is designed to accomplish the following. First, the extent of phenotypic by performing fluorometric assays for XDH. Second, these strains will be subjected to rocket immunoelectrophoresis to quantitate differences in the number of XDH molecules. Third, these strains will be assayed for XDH structural variation by sequential polyacrylamide gele electrophoresis. Finally, since these lines already have been characterized extensively for restriction sites around the structural gene are being sequenced, the data from this proposed research will be used to study relationships among phenotypic variation, XDH protein variation, and DNA sequence variation in the control (regulatory) element as opposed to structural element of this enzyme-coding gene. The results will contribute toward the understanding of the relative phenotypic effects of mutations (caused by UV or high energy irradiation or chemical mutagens) in regulatory versus structural sequences in human populations.